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      Effects of esketamine on postoperative rebound pain in patients undergoing unilateral total knee arthroplasty: a single-center, randomized, double-blind, placebo-controlled trial protocol

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          Abstract

          Introduction

          Rebound pain, transient and acute postoperative pain after the disappearance of regional block anesthesia, has been a concern in recent years. Insufficient preemptive analgesia and hyperalgesia induced by regional block are the main mechanisms. At present, the evidence for the treatment of rebound pain is limited. The esketamine, as an antagonist of the N-methyl-D-aspartate receptor, has been proven to prevent hyperalgesia. Therefore, this trial aims to evaluate the impact of esketamine on postoperative rebound pain in patients undergoing total knee arthroplasty.

          Methods/design

          This study is a single-center, prospective, double-blind, randomized, placebo-controlled trial. Participants who plan to undergo total knee arthroplasty will be randomly assigned to the esketamine group ( N = 178) and placebo group ( N = 178) in a ratio of 1:1. This trial aims to evaluate the impact of esketamine on postoperative rebound pain in patients undergoing total knee arthroplasty. The primary outcome of this trial is the incidence of rebound pain within 12 h after the operation in the esketamine group and the placebo group. The secondary outcome will be to compare (1) the incidence of rebound pain 24 h after the operation; (2) the time to enter the pain cycle for the first time within 24 h after the procedure; (3) the first time of rebound pain occurred within 24 h after surgery; (4) the modified rebound pain score; (5) NRS score under rest and exercise at different time points; (6) the cumulative opioid consumption at different time points; (7) patient’s prognosis and knee joint function evaluation; (8) blood glucose and cortisol concentration; (9) patient’s satisfaction score; (10) adverse reactions and adverse events.

          Discussion

          The effect of ketamine on preventing postoperative rebound pain is contradictory and uncertain. The affinity of esketamine to the N-methyl-D-aspartate receptor is about four times higher than levo-ketamine, the analgesic effect is 3 times higher than levo-ketamine, and there are fewer adverse mental reactions. To our knowledge, there is no randomized controlled trial to verify the impact of esketamine on postoperative rebound pain in patients undergoing total knee arthroplasty. Therefore, this trial is expected to fill an important gap in relevant fields and provide novel evidence for individualized pain management.

          Clinical Trial Registration

          http://www.chictr.org.cn, identifier ChiCTR2300069044.

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          Most cited references28

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          Postoperative Pain Management in Total Knee Arthroplasty

          Total knee arthroplasty (TKA) is one of the most common surgeries performed to relieve joint pain in patients with end‐stage osteoarthritis or rheumatic arthritis of the knee. However, TKA is followed by moderate to severe postoperative pain that affects postoperative rehabilitation, patient satisfaction, and overall outcomes. Historically, opioids have been widely used for perioperative pain management of TKA. However, opioids are associated with undesirable adverse effects, such as nausea, respiratory depression, and retention of urine, which limit their application in daily clinical practice. The aim of this review was to discuss the current postoperative pain management regimens for TKA. Our review of the literature demonstrated that multimodal analgesia is considered the optimal regimen for perioperative pain management of TKA and improves clinical outcomes and patient satisfaction, through a combination of several types of medications and delivery routes, including preemptive analgesia, neuraxial anesthesia, peripheral nerve blockade, patient‐controlled analgesia and local infiltration analgesia, and oral opioid/nonopioid medications. Multimodal analgesia provides superior pain relief, promotes recovery of the knee, and reduces opioid consumption and related adverse effects in patients undergoing TKA.
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            Perioperative intravenous ketamine for acute postoperative pain in adults

            Inadequate pain management after surgery increases the risk of postoperative complications and may predispose for chronic postsurgical pain. Perioperative ketamine may enhance conventional analgesics in the acute postoperative setting.
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              Subacute pain and function after fast-track hip and knee arthroplasty.

              In a well-defined fast-track setup for total hip and knee arthroplasty, with a multimodal analgesic regimen consisting of intra-operative local anaesthetic infiltration and oral celecoxib, gabapentin and paracetamol for 6 days postoperatively, we conducted a prospective, consecutive, observational study. The purpose was to describe the prevalence and intensity of subacute postoperative pain and opioid related side effects, use of analgesics and functional ability 1-10 and 30 days postoperatively. Fast-track total hip and knee arthroplasty with early discharge ( 95% of patients after discharge before day 10 after total hip arthroplasty. However, after total knee arthroplasty 52% patients reported moderate pain (VAS 30-59 mm), and 16% severe pain (VAS > or = 60 mm) when walking 1 month after surgery with a concomitant increase in the use of strong opioids. These results emphasise the need for improvement in analgesia after discharge following total knee arthroplasty, to facilitate rehabilitation.
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                Author and article information

                Contributors
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                27 April 2023
                2023
                : 14
                : 1179673
                Affiliations
                [1] 1Department of Anesthesiology, The Affiliated Hospital of Qingdao University , Qingdao, China
                [2] 2Department of Joint Surgery, The Affiliated Hospital of Qingdao University , Qingdao, China
                [3] 3Phase I Clinical Trial Center, The Affiliated Hospital of Qingdao University , Qingdao, China
                Author notes

                Edited by: Kabirullah Lutfy, Western University of Health Sciences, United States

                Reviewed by: You Shang, Huazhong University of Science and Technology, China; Mohammad Ali Sahmeddini, Shiraz University of Medical Sciences, Iran

                *Correspondence: Yang Zhao, zhaoy1979@ 123456qdu.edu.cn

                These authors have contributed equally to this work

                Article
                10.3389/fneur.2023.1179673
                10174246
                37181565
                d9bcb735-4919-4eda-b86f-fda89ee6e435
                Copyright © 2023 Zhu, Li, Liu, Sheng, Zhang, Jiang, Li, He, Zou, Zhang, Wang, Jiang and Zhao.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 08 March 2023
                : 10 April 2023
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 28, Pages: 12, Words: 8837
                Categories
                Neurology
                Study Protocol
                Custom metadata
                Experimental Therapeutics

                Neurology
                total knee arthroplasty,esketamine,rebound pain,postoperative acute pain,hyperalgesia
                Neurology
                total knee arthroplasty, esketamine, rebound pain, postoperative acute pain, hyperalgesia

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